Early pregnancy complications

“Two or more abortions could more than double chances of a premature birth next time,” the Daily Mail has reported. Numerous news sources have reported on new research that has linked early pregnancy complications to problems later in pregnancy or in subsequent pregnancies.

This news story is based on a detailed review of a number of studies on pregnancy complications and outcomes. It looked at the link between different early pregnancy complications in a current or previous pregnancy, including prior miscarriage or termination, and adverse outcomes related to later pregnancy and birth. The review identified studies that noted several significant associations in early complications and later problems, in particular risk of premature delivery and low birth weight.

However, the authors note that there are a number of important limitations which must be taken into account when considering their findings. In particular, some figures quoted in the review come from individual studies of variable quality. Nevertheless, these findings indicate the importance of recognising any issues or complications of current and previous pregnancies so that all expectant mothers and their babies receive appropriate monitoring, care and support.

Where did the story come from?

This research was conducted by Dr Robert van Oppenraaij of Erasmus University Medical Centre in the Netherlands and colleagues of the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group for Early Pregnancy (SIGEP). No sources of funding were reported.

The study was published in the peer-reviewed medical journal Human Reproduction Update . The findings were presented by Dr van Oppenraaij at the 25th annual meeting of the ESHRE in Amsterdam.

What kind of scientific study was this?

This was a systematic review of literature which investigated the possible link between complications during early pregnancy and adverse pregnancy and birth outcomes.

The researchers searched the Medline and Cochrane literature databases for observational studies, which had examined any complications during the first 12 weeks (first trimester) of pregnancy. These included miscarriage or termination of a previous pregnancy and complications of the current pregnancy, including threatened miscarriage, morning sickness, crown-rump length discrepancy and apparent loss of a twin that was previously detected.

The authors looked for studies where data on these complications were combined with documentation of adverse outcomes in later pregnancy and birth. The outcomes they included in their search were numerous, including pre-eclampsia, placenta praevia (placenta positioned over the cervix), premature rupture of membranes, premature delivery and adverse outcomes in the newborn, such as death within 30 days of delivery.

From the studies, they extracted the risk figures for an adverse pregnancy outcome resulting from early pregnancy complications. The review examined each early pregnancy complication and its associated outcomes in depth and discussed possible reasons for this apparent link.

The researchers graded each link they found according to the consistency their finding had with the studies that provided the strongest level of evidence. This grading ranged from ‘A’ (consistent evidence from high-quality studies) to ‘D’ (inconsistent or inconclusive studies of any level). The review did not carry out statistical pooling of the results of the studies it identified, as the studies were reported to be too different to allow this approach. Odds ratios or relative risks of outcomes were reported from the “best and largest” individual studies.

The review provided a large number of detailed findings, a summary of which follows.

What were the results of the study?

The review found a significant increase (at least doubling) in the risk of the following outcomes after the associated complication in a previous pregnancy:

Increased risk of infant death around the time of birth following a single miscarriage in a previous pregnancy.
Increased risk of very premature delivery (birth at less than 34 weeks of pregnancy) following two or more previous miscarriages.
Increased risk of very premature delivery following two or more previous terminations of pregnancy.
Increased risk of placenta praevia, premature preterm rupture of membranes and low infant birth weight after recurrent miscarriage.

The review found a significant increase (at least doubling) in the risk of the following outcomes in a current pregnancy after the associated complication:

Increased risk of low (less than 2.5kg) and very low (less than 1.5kg) birth weight after a threatened miscarriage.
Increased risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, premature delivery, infant small for gestational age and low 5-minute Apgar score (a scoring system that assesses the immediate health and responsiveness of the newborn) after detection of an intrauterine haematoma.
Increased risk of very premature delivery and intrauterine growth restriction after a crown-rump length discrepancy.
Increased risk of very premature delivery and low and very low birth weight following a ‘vanishing twin phenomenon’.
Increased risk of premature delivery (birth at less than 37 weeks), low birth weight and low 5-minute Apgar score in a pregnancy complicated by severe morning sickness (note that risk of miscarriage is significantly decreased in a pregnancy with morning sickness).

For a number of other specific outcomes, there was either no data about the association with early complications or no significant association.

What interpretations did the researchers draw from these results?

On the basis of their review, the authors conclude that specific events and complications during the first 12 weeks of pregnancy are predictors of subsequent adverse outcomes later in pregnancy and at the time of birth. However, they acknowledge that some of these associations are based on limited or small uncontrolled studies and that larger, population-based controlled studies will be needed to confirm these associations.

What does the NHS Knowledge Service make of this study?

This detailed review has identified a number of available studies which have examined the link between early pregnancy complications and adverse outcomes, both later in that same pregnancy and in future pregnancies.

The review identified studies that noted several significant associations. Although some of the associations are derived from large, high-quality studies, there are important limitations when considering certain pregnancy complications individually.

For example, termination of pregnancy may be carried out by either medical or surgical means at different times in a pregnancy and for various reasons (for example, due to an unwanted pregnancy or medical complications with the mother or developing foetus). This review considered all types of termination as a single risk factor and did not take into account how the range of reasons or methods involved may differently affect associated outcomes in a later pregnancy.

Equally, the main review only presented the overall relative risk figures (i.e. how many times more likely an event was) rather than the absolute size of the risk. From these figures we know how likely an outcome is following a particular complication compared to not having the complication, but the figure does not tell us how common that outcome will actually be among all pregnant women.

Absolute risk figures can be obtained by consulting the supplemental data provided alongside the main review and the individual studies themselves, but this data is too extensive to summarise here. Absolute risk figures were variable but, in general, they were still quite low. For example, incidence of low infant birth weight was 9.4% in women who had had two or more miscarriages compared to 4.5% in women who had not, and 2.8% in women who had had a previous termination compared to 1.4% in women who had not had a termination.

There are several other points to note when interpreting this study:

The studies included in the review are likely to be of variable quality and have different sizes, methods, assessment methods and the possibility of bias. The authors avoided combining them to give a pooled estimate of the risk of an outcome.
The relative risk figures reported in the review were taken from a single study, which was the best and largest study identified. However, as the authors observe, the majority of studies from which these risk figures came were what they graded as B or C, i.e. evidence from moderate or poorer-quality studies or extrapolations of findings from studies of higher quality.
There are various possible confounding factors linked to both early pregnancy and later pregnancy complications, which may or may not have been taken into account by the different studies when they were examining risk. These include maternal age, smoking, alcohol or drug abuse, socioeconomic status or medical comorbidity.
As the authors say, larger, controlled studies using National Birth Registries are needed to further examine these associations.

Even though some of the associations are only supported by limited evidence and are not confirmed, they nevertheless indicate the importance of recognising any issues or complications that expectant mothers and their babies may face. This will enable them to receive appropriate monitoring, care and support.

As Dr van Oppenraaij said in the press conference, “While it is true that most conditions are difficult to prevent, with improved monitoring in high-risk pregnancies it is possible to reduce perinatal or postnatal foetal complications.”